It has long been known that after exercise glucose utilization and glycogen synthesis in skeletal muscle are enhanced. We have recently demonstrated that another post-exercise change in muscle is an altered response to insulin. Thus, using intact rats and a perfused hindquarter preparation, we found that the stimulation of glucose and AIB transport and glycogen synthesis by insulin were enhanced after voluntary exercise or electrical stimulation. In addition after intense exercise insulin increased 0-2 consumption, an effect it did not have in resting muscle. The overall objectives of this proposal are to examine this characterization of the post-exercise state and to explore the physiological relevance and possible mechanisms for the increase in insulin effect. Using the perfused rat hindquarter, the intact rat and man, we will carry out studies with the following specific aims: (1) To characterize further the effects of prior exercise on insulin action in muscle. The basis for the enhanced ability of insulin to stimulate glycogen synthesis in the hindquarter preparation will be examined, as will the effects of prior exercise on the ability of insulin to stimulate protein synthesis and activate pyruvate dehydrogenase and glycogen synthase; (2) To study possible mechanisms for the post-exercise increase in insulin sensitivity. Insulin binding and insulin-stimulated phosphorylation of the insulin receptor will be examined in muscle, as will the effect of exercise itself on receptor phosphorylation. (3) To determine whether prior exercise increases insulin sensitivity in vivo. Whole body and individual organ insulin sensitivity will be assessed in the conscious rat using an insulin-glucose clamp technique developed by one of the applicants. (4) To examine the basis for increased thermogenesis in the post-exercise state. Processes that could contribute to the insulin-induced increase in thermogenesis in the perfused hindquarter will be studied. In addition we will assess physiological determinants and possible mechanisms for the post-exercise increase in dietary-induced thermogenesis we have observed in humans. These studies should help delineate the array of metabolic alterations produced by insulin in the post-exercise state. They should also cast light on the mechanisms by which sensitivity and insulin-induced thermogenesis in muscle are enhanced by prior exercise.